Patients with Parkinson's disease demonstrate deficits in visual‐spatial memory in the Chinese Visual Retention Test

Abstract Objective We aimed to explore the existence of visual‐spatial memory deficit in patients with Parkinson's disease (PD) without dementia in the Chinese Visual Retention Test, as well as to assess whether their performance is related to age, duration, severity, stage, and dopamine (DA) dose. Methods Forty‐two patients with PD and 30 healthy controls were included in our study. The Chinese Visual Retention Test was used to evaluate the visual‐spatial memory of the subjects. Parameters of the Chinese Visual Retention Test were compared between the two groups. Correlation analysis and multiple linear regression analysis were used to explore the associations of the Chinese Visual Retention Test with age, duration, severity, stage of PD, and DA dose. Results Three correct scores in the Chinese Visual Retention Test were all significantly lower in the PD group than in the control group. The total error scores, error scores of omissions, deformation, and persistence in the PD group were significantly higher than those in the control group. Correlation analysis showed the total error scores in the Chinese Visual Retention Test was positively correlated with UPDRS III score and H‐Y classification. Multiple linear regression analysis showed that the total error scores in the Chinese Visual Retention Test were associated with the UPDRS III score and H‐Y classification. Conclusion Patients with PD without dementia had visual‐spatial memory deficits in the Chinese Visual Retention Test which may be affected by the severity and clinical stage of PD.

can often be debilitating for patients and their caregivers (Lawson et al., 2016).
Visual-spatial memory abilities have been reported to predict progressive cognitive impairment and PD dementia (Yang et al., 2018).
Several previous studies (Del Pino et al., 2021;Fernandez-Baizan et al., 2020;Netherton et al., 1989) have reported that patients with PD present significant impairment in visual-spatial memory abilities.However, the evaluation of the visual-spatial memory abilities in patients with PD has not been consistent.
The Benton Visual Retention Test was developed in 1955 and has been widely used to evaluate cognitive function (Didycz et al., 2018;Talarowska et al., 2011).Further, Netherton et al. (1989) found that PD was associated with changes in visual-spatial memory which was predicted by age.The Chinese Visual Retention Test (Tang & Gong, 1993) was translated and adapted from the Benton Visual Retention Test, which details the implementation methods, scoring principles, validity, and reliability.
Our study explored the existence of visual-spatial memory impairment in patients with PD without dementia using the Chinese Visual Retention Test, as well as assessed whether their performance is related to their age, duration, severity, stage of PD, and dopamine (DA) dose.

Subjects
This case-control study was conducted between October 2015 and July 2017 at the Department of Neurology of Zhoushan Hospital.
Forty-two patients with PD and 30 age-matched healthy controls were included.Written informed consent was obtained from all subjects.
The study was approved by the Ethics Committee of Zhoushan Hospital (Liu et al., 2017).Forty of the patients with PD were treated with levodopa or a DA agonist.PD was diagnosed according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for PD (Postuma et al., 2015).The exclusion criteria were patients with (1) dementia, severe anxiety, depression, or psychosis, (2) structural damage in the retina or ophthalmologic disease, and (3) other severe diseases, such as cancer, heart failure, renal failure, and chronic obstructive pulmonary disease.(Liu et al., 2017).Patients were assessed in the "on" state before the morning dose of the drug.The DA dose, also known as levodopa-equivalent dose (LED), was calculated using the formula (Tomlinson et al., 2010).Ophthalmologic evaluations were performed at the eye clinic and included a visual acuity test (Snellen table), an Ishihara color test, biomicroscopy, and intraocular pressure measurement using the Goldmann applanation tonometer (Liu et al., 2017).Optical coherence tomography (OCT)

METHODS
was used to evaluate the retinal structure.
The Chinese Visual Retention Test evaluation includes three different series: Series C, Series D, and Series E. Each series includes 10 cards, each of which has one or more graphics.In this study, methods C, B, and D were used sequentially for each series, of which the correct and error points were recorded.There are six types of errors: omission, deformation, persistence, rotation, dislocation, and incorrect size.
Each type of error is scored as one point to determine the total error score. The

Abnormality in the Chinese Visual Retention Test
The results of the Chinese Visual Retention Test showed that the correct scores for methods C, B, and D were all significantly lower in the PD group than in the control group (U = 397.5,Z = −2.729,p = .006;   2 and Figure 1).The total error scores, as well as error scores of omissions, deformation, and persistence were significantly higher in the PD group than in the control group (t = 2.972, p = .004;t = 2.402; p = .019;t = 2.148, p = .035;t = 2.345; p = .022,respectively) (Table 2 and   Figure 2).There were no significant differences in the error scores of rotation, dislocation, and incorrect size between the two groups (p all > .05).

The correlation of the Chinese Visual Retention Test with PD
In the PD group, the total error scores in the Chinese Visual Retention Test were positively correlated with the UPDRS III score (r = 0.446, p < .01)(Figure 3) and H-Y classification (r s = 0.637, p < .01)(Figure 3), but not with age, PD duration, and DA dose.The result of multiple linear regression analysis showed that the total error scores in the Chinese Visual Retention Test were associated with the UPDRS III score (B = 0.367, p < .05,Table 3) and H-Y classification (B = 7.258, p < .01,Table 3).

DISCUSSION
Although previous studies on visual-spatial memory in PD are scarce, some have shown that patients express subjective complaints in their daily spatial activities, such as reading a map, using navigation devices, or finding their way while driving (Davidsdottir et al., 2005) Older age is considered a significant predictor of poor cognitive performance in PD patients (Hu et al., 2014;Oikonomou et al., 2021;Vingerhoets et al., 2003).One possible reason is that age affects the progress of PD, and older patients tend to progress quickly and can rapidly develop into dementia.Contrary to these studies, our study showed no association between visual-spatial memory deficits and age.
Age itself may not be an independent risk factor for visual-spatial memory deficit.In agreement with previous studies (Oikonomou et al., 2021;Shuncai et al., 2016), our study also suggest PD duration and DA dose are not independent risk factors for visual-spatial memory deficit.
The etiology of PD is multifactorial, and progressive loss of dopaminergic neurons in the substantia nigra is widely accepted.However, DA appears to be more involved than the substantia nigra.Information processing, such as planning, problem-solving, decision-making, and response selection, is associated with the function of frontostriatal circuits.Recent studies have attempted to link cognitive symptoms with specific neuronal circuits in the basal ganglia and its connections.Cognitive deficits in PD may be linked to a malfunction of frontal-basal ganglia neural circuits, which are important for executive functions.Nevertheless, frontal-basal ganglionic dysfunction only partially accounts for the visual-spatial memory deficits present in PD (Liu et al., 2015).It has been proposed that the loss of DA in the substantia nigra and striatum affects an extensive neural network, including prefrontal structures, via mesolimbic-frontal fibers.All these factors may contribute to visual-spatial memory deficits and progressive cognitive dysfunction in PD patients.
Given the high prevalence rates of dementia in PD, prediction of the risk of its progression seems highly important.However, there are lack of effective early biomarkers for the diagnosis of dementia in PD.Our study suggests that visual-spatial memory deficits occur in the early stages of cognitive impairment in patients with PD.As cognitive impairment appears in the early stages of PD, the guidelines for PD-mild cognitive impairment (PD-MCI) (Goldman et al., 2013) complement the current criteria defining PD.Deficits in visual-spatial skills can be considered a prodromal symptom of PD (Kehagia et al., 2013).The results of our study also suggest that visual-spatial memory impairment may be a predictor of progression of cognitive impairment and that visual-spatial memory tests may be beneficial for the diagnosis of PD.
The limitations of our study are as follows: (1) Our study included a small number of patients with PD and controls, which may not conclusively support our findings.
(2) PD patients with retinal impairment were excluded; therefore, we were unable to determine the relationship between retinal impairment and deficits in visual-spatial memory.

CONCLUSION
Patients with PD without dementia already had visual-spatial memory deficits in the Chinese Visual Retention Test.Further, impaired visualspatial memory may be affected by the severity and clinical stage of PD.

F
I G U R E 1 (a) Comparison of the correct scores of method C between the PD group and the controls.(b) Comparison of the correct scores of method B between the PD group and the controls.(c) Comparison of the correct scores of method D between the PD group and the controls.t = −3.244,p = .002;t = −3.132;p = .003,respectively) (Table

F
I G U R E 2 (a) Comparison of the total error scores of the Chinese Visual Retention Test between the PD group and the controls.(b) Comparison of omission error scores between the PD group and the controls.(c) Comparison of deformation error scores between the PD group and the controls.(d) Comparison of persistence error scores of persistence between the PD group and the controls.FI G U R E 3 (a) Correlation of the total error scores of the Chinese Visual Retention Test and UPDRS III scores in PD group.(b) Correlation of the total error scores of the Chinese Visual Retention Test and H-Y classification in PD group.

TA B L E 1
Demographic and clinical data of subjects.Intergroup comparison of the Chinese Visual Retention Test.
Multiple linear regression analysis of factors associated with the Chinese Visual Retention Test.
. Our findings suggest that patients with PD without dementia already have visual-spatial memory deficits according to the Chinese Visual Retention Test, which was related to the severity of motor symptoms and clinical stage of PD.TA B L E 3